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Filter articles published since 2015 by topic, disease, or article type.

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Results are filtered to show all matching articles from a particular category, and to show only articles that match all selected categories.

For instance, if "Biomarkers" and "Genetics" are selected in the Topic category, and "Multiple sclerosis" is selected in the Disease category, all results that match EITHER the Biomarkers OR Genetics Topic category will be shown, but only if they also match the Multiple sclerosis Disease category; i.e. Boolean search of [("Biomarkers" OR "Genetics") AND "multiple sclerosis"]

Ataxin-2 ASOs May Clear More Obstacles In ALS

Researchers are developing potential treatment strategies for ALS that target nuclear export in hopes to prevent key proteins including TDP-43 from building up in the cytoplasm of motor neurons (see April 2018 news). But according to a study led by the University of Michigan’s Sami Barmada, TDP-43 may exit the nucleus through multiple mechanisms suggesting that other approaches may be needed to reduce motor neuron toxicity in the disease (see April 2018 news; Archbold et al., 2018).

All clear. Treatment with Ataxin-2 ASOs restored the transport of proteins in and out of the nucleus of motor neurons, potentially reducing toxicity. [Courtesy of Zhang et al., 2018, Cell].

Now, a research team led by Johns Hopkins University’s Jeffrey Rothstein and Thomas Lloyd in Baltimore, Maryland report that increased stress in motor neurons may lead to a disruption in nucleocytoplasmic transport in ALS. And, reducing the buildup of key RNA granules that assemble during these tough times may help protect motor neurons in part, by clearing up these nuclear traffic jams.

The study found that during increased stress, key proteins needed to transport cargo between the nucleus and cytoplasm became sequestered into stress granules slowing nuclear traffic to a crawl – at least in iPS-derived C9orf72 ALS motor neurons (see figure). Blocking the assembly of these RNA granules by lowering levels of ataxin-2 restored nucleocytoplasmic transport, potentially reducing toxicity.

The results build on previous studies led by Aaron Gitler at Stanford University School of Medicine, which found that a single ataxin-2 antisense oligonucleotide treatment, delivered directly into the brain at the neonatal stage, improved motor function and increased the survival time of ALS model mice by more than 33% (see May 2017 news; Becker et al., 2017).

Together, the results suggest that reducing levels of ataxin-2 may help protect motor neurons in ALS by reducing the build-up of key proteins in the cytoplasm including TDP-43.

The findings come at the heels of a previous study led by Mayo Clinic’s Wilfried Rossoll in Jacksonville, Florida, which suggest that nuclear pores, the key gateway that mediates traffic in and out of the nucleus, become damaged in ALS through a TDP-43-based mechanism (see Jan 2018 news; Chou et al., 2018).

Efforts are underway to further evaluate ataxin-2 ASOs as a treatment for ALS, including sporadic disease (see May 2017 news). Stay tuned.

Filter articles published since 2015 by topic, disease, or article type.

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Results are filtered to show all matching articles from a particular category, and to show only articles that match all selected categories.

For instance, if "Biomarkers" and "Genetics" are selected in the Topic category, and "Multiple sclerosis" is selected in the Disease category, all results that match EITHER the Biomarkers OR Genetics Topic category will be shown, but only if they also match the Multiple sclerosis Disease category; i.e. Boolean search of [("Biomarkers" OR "Genetics") AND "multiple sclerosis"]